Hemoglobin Concentration Impacts Viscoelastic Hemostatic Assays in ICU Admitted Patients.

OBJECTIVES: Low hemoglobin concentration impairs clinical hemostasis across several diseases. It is unclear whether hemoglobin impacts laboratory functional coagulation assessments. We evaluated the relationship of hemoglobin concentration on viscoelastic hemostatic assays in intracerebral hemorrhage (ICH) and perioperative patients admitted to an ICU. DESIGN: Observational cohort study and separate in vitro laboratory study. SETTING: Multicenter tertiary referral ICUs. PATIENTS: Two acute ICH cohorts receiving distinct testing modalities: rotational thromboelastometry (ROTEM) and thromboelastography (TEG), and a third surgical ICU cohort receiving ROTEM were evaluated to assess the generalizability of findings across disease processes and testing platforms. A separate in vitro ROTEM laboratory study was performed utilizing ICH patient blood samples. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Relationships between baseline hemoglobin and ROTEM/TEG results were separately assessed across patient cohorts using Spearman correlations and linear regression models. A separate in vitro study assessed ROTEM tracing changes after serial hemoglobin modifications from ICH patient blood samples. In both our ROTEM (n = 34) and TEG (n = 239) ICH cohorts, hemoglobin concentrations directly correlated with coagulation kinetics (ROTEM r: 0.46; p = 0.01; TEG r: 0.49; p < 0.0001) and inversely correlated with clot strength (ROTEM r: -0.52, p = 0.002; TEG r: -0.40, p < 0.0001). Similar relationships were identified in perioperative ICU admitted patients (n = 121). We continued to identify these relationships in linear regression models. When manipulating ICH patient blood samples to achieve lower hemoglobin concentrations in vitro, we similarly identified that lower hemoglobin concentrations resulted in progressively faster coagulation kinetics and greater clot strength on ROTEM tracings. CONCLUSIONS: Lower hemoglobin concentrations have a consistent, measurable impact on ROTEM/TEG testing in ICU admitted patients, which appear to be artifactual. It is possible that patients with low hemoglobin may appear to have normal viscoelastic parameters when, in fact, they have a mild hypocoagulable state. Further work is required to determine if these tests should be corrected for a patient's hemoglobin concentration.

Perioperative fluid management and outcomes in adult deceased donor liver transplantation - A systematic review of the literature and expert panel recommendations.

BACKGROUND: Fluid management practices during and after liver transplantation vary widely among centers despite better understanding of the pathophysiology of end-stage liver disease and of the effects of commonly used fluids. This reflects a lack of high quality trials in this setting, but also provides a rationale for both systematic review of all relevant studies in liver recipients and evaluation of new evidence from closely related domains, including hepatology, non-transplant abdominal surgery, and critical care. OBJECTIVES: To develop evidence-based recommendations for perioperative fluid management to optimize immediate and short-term outcomes following liver transplantation. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Studies included those evaluating the following postoperative outcomes: acute kidney injury, respiratory complications, operative blood loss/red cell units required, and intensive care length of stay. PROSPERO protocol ID: CRD42021241392 RESULTS: Following expert panel review, 18 of 1624 screened studies met eligibility criteria for inclusion in the final quantitative synthesis. These included six single center RCTs, 11 single center observational studies, and one observational study comparing centers with different fluid management techniques. Definitions of interventions and outcomes varied between studies. Recommendations are therefore based substantially on expert opinion and evidence from other clinical settings. CONCLUSIONS: A moderately restrictive or "replacement only" fluid regime is recommended, especially during the dissection phase of the transplant procedure. Sustained hypervolemia, based on absence of fluid responsiveness, elevated filling pressures and/or echocardiographic findings, should be avoided (Quality of Evidence: Moderate | Grade of Recommendation: Weak for restrictive fluid regime. Strong for avoidance of hypervolemia). Mean Arterial Pressure (MAP) should be maintained at >60-65 mmHg in all cases (Quality of Evidence: Low | Grade of Recommendation: Strong). There is insufficient evidence in this population to support preferential use of any specific colloid or crystalloid for routine volume replacement. However, we recommend against the use of 130/.4 HES given the high incidence of AKI in this population.

A2A adenosine receptor activation prevents neutrophil aging and promotes polarization from N1 towards N2 phenotype.

Extracellular adenosine is a biologically active signaling molecule that accumulates at sites of metabolic stress in sepsis. Extracellular adenosine has potent immunosuppressive effects by binding to and activating G protein-coupled A2A adenosine receptors (A2AARs) on the surface of neutrophils. A2AAR signaling reproduces many of the phenotypic changes in neutrophils that are characteristic of sepsis, including decreased degranulation, impaired chemotaxis, and diminished ability to ingest and kill bacteria. We hypothesized that A2AARs also suppress neutrophil aging, which precedes cell death, and N1 to N2 polarization. Using human neutrophils isolated from healthy subjects, we demonstrate that A2AAR stimulation slows neutrophil aging, suppresses cell death, and promotes the polarization of neutrophils from an N1 to N2 phenotype. Using genetic knockout and pharmacological blockade, we confirmed that A2AARs decrease neutrophil aging in murine sepsis induced by cecal ligation and puncture. A2AARs expression is increased in neutrophils from septic patients compared to healthy subject but A2AAR expression fails to correlate with aging or N1/N2 polarization. Our data reveals that A2AARs regulate neutrophil aging in healthy but not septic neutrophils.

Spinal Cord Protection for Thoracoabdominal Aortic Surgery.

Open and endovascular repairs of the descending thoracic and thoracoabdominal aorta are associated with a substantial risk of spinal cord injury, namely paraplegia. Endovascular repairs seem to have a lower incidence of spinal cord injury, but there have been no randomized trials comparing outcomes of open and endovascular repairs. Paraplegia occurs when collateral blood supply to the anterior spinal artery is impaired. The risk of spinal cord injury can be mitigated with perioperative protocols that include drainage of cerebrospinal fluid, avoidance of hypotension and anemia, intraoperative neurophysiologic monitoring, and advanced surgical techniques. Drainage of cerebrospinal fluid using a spinal drain decreases the risk of spinal cord ischemia by improving spinal cord perfusion pressure. However, cerebrospinal fluid drainage has risks including neuraxial and intracranial bleeding, and these risks need to be carefully weighed against its potential benefit. This review discusses current surgical management of descending thoracic and thoracoabdominal aortic disease, incidence of and risk factors for spinal cord injury, and elements of spinal cord protection protocols that pertain to anesthesiologists, with a focus on cerebrospinal fluid drainage.

Clinical considerations for the evaluation of patients with left ventricular assist devices.

ABSTRACT: A left ventricular assist device (LVAD) provides mechanical circulatory support for patients with end-stage heart failure. As these devices become more prevalent, clinicians must be familiar with the device's function, common complications, and management strategies when evaluating this patient population.

Acute kidney injury after cardiac surgery: A comparison of different definitions.

AIM: Acute kidney injury (AKI) after cardiac surgery increases morbidity and mortality. Different definitions for AKI have been used such as Acute Kidney Injury Network (AKIN), Kidney Disease: Improving Global Outcomes (KDIGO) or risk, injury, failure, loss, end-stage kidney disease (RIFLE). The aim of this study is to determine the best definition of AKI after cardiac surgery with the largest impact on the outcome. METHODS: This retrospective study of cardiac surgery patients compared the incidence and effect on outcome (90-day and 1-year mortality) of different definitions of AKI: RIFLE, AKIN and KDIGO. Additionally, we defined transient AKI (increase in serum creatinine that resolved in <72 hours), sustained (increase in serum creatinine within 48 hours that remained for >72 hours), and late (increase in serum creatinine after 48 hours). RESULTS: Of the included 1551 patients, 410 patients developed AKI defined by AKIN criteria, 449 defined by KDIGO and 217 defined by RIFLE-Risk criteria. Hundred and nine patients developed transient AKI (6.9%), 183 patients had sustained AKI (11.6%), and 106 patients had late AKI (6.7%). The best definition with the highest positive likelihood ratio was RIFLE-Risk (positive likelihood ratio = 2.32) followed by "sustained AKI" (positive likelihood ratio = 2.27). AKI defined by AKIN criteria missed all 80 patients with late AKI and 39 patients with KDIGO AKI. CONCLUSION: Risk, injury, failure, loss, end-stage kidney disease-risk was the best definition of AKI as determined by the ability to predict short-term mortality. A substantial number of patients developed AKI only after 48 hours, and these were missed when using AKIN criteria. AKIN criteria are not sensitive enough to capture all episodes of AKI in this population.

Functional Coagulation Differences Between Lobar and Deep Intracerebral Hemorrhage Detected by Rotational Thromboelastometry: A Pilot Study.

BACKGROUND: Lobar intracerebral hemorrhage (ICH) is known to have better clinical outcomes and preliminary evidence of less hematoma expansion compared to deep ICH. No functional coagulation differences between lobar and deep ICH have been identified using traditional plasma-based coagulation tests. We investigated for coagulation differences between lobar and deep ICH using whole-blood coagulation testing (Rotational Thromboelastometry: [ROTEM]). METHODS: Clinical, radiographic, and laboratory data were prospectively collected for primary ICH patients enrolled in a single-center ICH study. Patients with preceding anticoagulant use or admission coagulopathy on traditional laboratory testing were excluded. Lobar and deep ICH patients receiving admission ROTEM were analyzed. Linear regression was used to assess the association of ICH location with coagulation test results after adjusting for potential confounders. RESULTS: There were 12 lobar and 19 deep ICH patients meeting inclusion criteria. Lobar ICH patients were significantly older and predominantly female. Lobar ICH had faster intrinsic pathway coagulation times (139.8 vs 203.2 s; 95% CI - 179.91 to - 45.96; p = 0.002) on ROTEM testing compared to deep ICH after adjusting for age, sex, and hematoma volume. This revealed functional coagulation differences, specifically quicker clot formation in lobar compared to deep ICH. No differences were noted using traditional coagulation testing (prothrombin time/partial thromboplastin time/platelet count). CONCLUSIONS: Our pilot data may suggest that there are functional coagulation differences between lobar and deep ICH identified using ROTEM. Whole-blood coagulation testing may be useful in assessing coagulopathy in ICH patients and in determining reversal treatment paradigms, though further work is needed.

Pulmonary alveolar hemorrhage in a patient with a temporary external ventricular assist device and extracorporeal membrane oxygenation.

Mechanical circulatory support is increasingly used and may bring about unique challenges. Most support systems require systemic anticoagulation and the need for anticoagulation must be balanced against the increased risk for bleeding. We report the case of a young man awaiting heart retransplantation, who was supported with a temporary extracorporeal ventricular assist device with the addition of an oxygenator. He developed hemoptysis that forced the cessation of anticoagulation exposing to increased thromboembolic risk. We discuss this distinct clinical scenario with no clearly defined solution and explore the risks and benefits of the different treatment options.

Unique Transcriptional Programs Identify Subtypes of AKI.

Two metrics, a rise in serum creatinine concentration and a decrease in urine output, are considered tantamount to the injury of the kidney tubule and the epithelial cells thereof (AKI). Yet neither criterion emphasizes the etiology or the pathogenetic heterogeneity of acute decreases in kidney excretory function. In fact, whether decreased excretory function due to contraction of the extracellular fluid volume (vAKI) or due to intrinsic kidney injury (iAKI) actually share pathogenesis and should be aggregated in the same diagnostic group remains an open question. To examine this possibility, we created mouse models of iAKI and vAKI that induced a similar increase in serum creatinine concentration. Using laser microdissection to isolate specific domains of the kidney, followed by RNA sequencing, we found that thousands of genes responded specifically to iAKI or to vAKI, but very few responded to both stimuli. In fact, the activated gene sets comprised different, functionally unrelated signal transduction pathways and were expressed in different regions of the kidney. Moreover, we identified distinctive gene expression patterns in human urine as potential biomarkers of either iAKI or vAKI, but not both. Hence, iAKI and vAKI are biologically unrelated, suggesting that molecular analysis should clarify our current definitions of acute changes in kidney excretory function.

Trans-diaphragmatic left ventricular venting during peripheral venous-arterial extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) has proven to be an invaluable method of cardiopulmonary support in cases of severe cardiogenic shock. In an emergency, femoral artery and vein cannulation is the easiest and quickest access to initiate support. Often, with peripheral venous-arterial ECMO (VA ECMO), an inadequate reduction in left ventricular end-diastolic pressure (LVEDP) is present secondary to increased afterload from retrograde flow, inadequate RV drainage or persistent bronchial circulation. Elevated LVEDP has been known to be associated with poor myocardial recovery, LV thrombus formation and significant pulmonary edema. A cannulation strategy to achieve partial ventricular unloading is of paramount importance when considering ECMO support following cardiogenic shock to increase the potential for myocardial recovery. We present a novel case of emergent peripheral VA ECMO cannulation with a trans-diaphragmatic left ventricular (LV) vent in a 61-year-old, 79 kg male with end-stage liver disease and hepatitis B cirrhosis who suffered cardiac arrest during orthotopic liver transplantation.

Rotational thromboelastometry predicts thromboembolic complications after major non-cardiac surgery.

INTRODUCTION: Thromboembolic complications contribute substantially to perioperative morbidity and mortality. Routine laboratory tests do not detect patients with acquired or congenital hypercoagulability who may be at increased risk of perioperative thromboembolism. Rotational thromboelastometry (ROTEM) is a digitized modification of conventional thromboelastography that is stable and technically easy to use. We designed a prospective observational study to evaluate whether preoperative ROTEM can identify patients at increased risk for postoperative thromboembolic complications after major non-cardiac surgery. METHODS: Preoperative ROTEM analysis using extrinsic rotational thromboelastometry (EXTEM), intrinsic rotational thromboelastometry (INTEM), and fibrinogen rotational thromboelastometry (FIBTEM) activators was performed on 313 patients undergoing major non-cardiac surgery. Patients' medical records were reviewed after discharge for results of standard coagulation studies - partial thromboplastin time (PTT), international normalized ratio (INR), platelet count - and evidence of thromboembolic complications during their hospital stay. A thromboembolic complication was defined as a new arterial or deep venous thrombosis, catheter thrombosis, or pulmonary embolism diagnosed by ultrasound or spiral chest computed tomography. RESULTS: Ten patients developed postoperative thromboembolic complications, of whom 9 had received standard prophylaxis with subcutaneous enoxaparin or heparin. There was no indication of by PTT, INR, or platelet count. Preoperative EXTEM and INTEM activators that assess fibrin clot formation and platelet interaction indicated that these patients had significantly lower clot formation time (CFT) and significantly higher alpha angle (α) and maximum clot firmness (MCF), compared to patients without thromboembolic complications. There was no significant difference for any parameter using FIBTEM activator, which excludes platelet interaction. Receiver operating characteristic (ROC) curves were constructed for these variables. INTEM clot firmness at 10 min (A10) was the best predictor of thromboembolic complications, with an ROC area under the curve of 0.751. CONCLUSIONS: Our results indicate that preoperative ROTEM assays that include fibrin clot and platelet interaction may detect patients at increased risk for postoperative thromboembolic complications after major non-cardiac surgery. Future studies need to evaluate the clinical utility and cost effectiveness of preoperative ROTEM and better define the association between ROTEM values and specific hypercoagulable conditions.

EVALUATION OF COMPONENTS OF THE EXTRACELLULAR PURINERGIC SIGNALING SYSTEM IN HUMAN SEPSIS.

ABSTRACT: Objective: Extracellular purines such as adenosine triphosphate (ATP), uridine triphosphate (UTP), and uridine diphosphate (UDP) and the ATP degradation product adenosine are biologically active signaling molecules, which accumulate at sites of metabolic stress in sepsis. They have potent immunomodulatory effects by binding to and activating P1 or adenosine and P2 receptors on the surface of leukocytes. Here we assessed the levels of extracellular purines, their receptors, metabolic enzymes, and cellular transporters in leukocytes of septic patients. Methods: Peripheral blood mononuclear cells (PBMCs), neutrophils, and plasma were isolated from blood obtained from septic patients and healthy control subjects. Ribonucleic acid was isolated from cells, and mRNA levels for purinergic receptors, enzymes, and transporters were measured. Adenosine triphosphate, UTP, UDP, and adenosine levels were evaluated in plasma. Results: Adenosine triphosphate levels were lower in septic patients than in healthy individuals, and levels of the other purines were comparable between the two groups. Levels of P1 and P2 receptors did not differ between the two patient groups. mRNA levels of ectonucleoside triphosphate diphosphohydrolase (NTPDase) 1 or CD39 increased, whereas those of NTPDase2, 3, and 8 decreased in PBMCs of septic patients when compared with healthy controls. CD73 mRNA was lower in PBMCs of septic than in healthy individuals. Equilibrative nucleoside transporter (ENT) 1 mRNA concentrations were higher and ENT2, 3, and 4 mRNA concentrations were lower in PBMCs of septic subjects when compared with healthy subjects. Concentrative nucleoside transporter (CNT) 1 mRNA levels were higher in PBMCs of septic versus healthy subjects, whereas the mRNA levels of CNT2, 3, and 4 did not differ. We failed to detect differences in mRNA levels of purinergic receptors, enzymes, and transporters in neutrophils of septic versus healthy subjects. Conclusion: Because CD39 degrades ATP to adenosine monophosphate (AMP), the lower ATP levels in septic individuals may be the result of increased CD39 expression. This increased degradation of ATP did not lead to increased adenosine levels, which may be explained by the decreased expression of CD73, which converts AMP to adenosine. Altogether, our results demonstrate differential regulation of components of the purinergic system in PBMCs during human sepsis.

Use of Transesophageal Echocardiography for Liver Transplantation: A Global Comparison of Practice From the ILTS, SATA, and LICAGE.

BACKGROUND: Anesthesiologists frequently use intraoperative transesophageal echocardiography (TEE) to aid in the diagnosis and management of hemodynamic problems during liver transplantation (LT). Although the use of TEE in US centers continues to increase, data regarding international use are lacking. METHODS: This prospective, global, survey-based study evaluates international experience with TEE for LT. Responses from 252 LT (105 US and 147 non-US) centers representing 1789 anesthesiologists were analyzed. RESULTS: Routine use of TEE in the United States has increased in the last 5 y (from 37% to 47%), but only 21% of non-US LT anesthesiologists use TEE routinely. Lack of training (44% US versus 70% non-US) and equipment (9% non-US versus 34% US) were cited as obstacles. Most survey participants preferred not to perform a complete cardiac examination but rather use only 6 of 11 basic views. Although non-US LT anesthesiologists more frequently had additional clinical training than their US counterparts, they had less TEE experience (13% versus 44%) and less frequently, TEE certification (22% versus 35%). Most LT anesthesiologists agreed that TEE certification is essential for proficiency. Of all respondents, 89% agreed or strongly agreed that TEE provides valuable information needed for immediate clinical decision-making, and >86% agreed or strongly agreed that that information could not be derived from other sources. CONCLUSIONS: The use of TEE for LT surgery in the US LT centers is currently higher compared with non-US LT centers. This may become a standard monitoring modality during LT in the near future.

Perioperative Considerations in Older Kidney and Liver Transplant Recipients: A Review.

With the growth of the older adult population, the number of older adults waitlisted for and undergoing kidney and liver transplantation has increased. Transplantation is an important and definitive treatment for this population. We present a contemporary review of the unique preoperative, intraoperative, and postoperative issues that patients older than 65 y face when they undergo kidney or liver transplantation. We focus on geriatric syndromes that are common in older patients listed for kidney or liver transplantation including frailty, sarcopenia, and cognitive dysfunction; discuss important considerations for older transplant recipients, which may impact preoperative risk stratification; and describe unique challenges in intraoperative and postoperative management for older patients. Intraoperative challenges in the older adult include using evidence-based best anesthetic practices, maintaining adequate perfusion pressure, and using minimally invasive surgical techniques. Postoperative concerns include controlling acute postoperative pain; preventing cardiovascular complications and delirium; optimizing immunosuppression; preventing perioperative kidney injury; and avoiding nephrotoxicity and rehabilitation. Future studies are needed throughout the perioperative period to identify interventions that will improve patients' preoperative physiologic status, prevent postoperative medical complications, and improve medical and patient-centered outcomes in this vulnerable patient population.